The 7α-methylestrone and derivatives thereof are important compounds as intermediates for manufacturing steroidal anticancer agents and like medicines, and diagnostic agents. Therefore, an effective production process thereof is demanded.
The steroid compound, such as 7α-methylestrone, that has the partial structure of ring A and ring B of its steroid skeleton as shown in Formula (2):

wherein R represents a hydrogen atom or C1-6 alkyl group;
is obtained from the steroid compound having the partial structure of ring A and ring B of its steroid skeleton as shown in Formula (1):

wherein R is the same as above.
Various methods for producing such steroid compounds in the manner as described above have been reported.
For example, Patent Document 1 discloses in Example 8 that, by using 11β-fluoro-7a-methylestra-4-ene-3,17-dione as a starting material and reacting it with copper (II) bromide in an acetonitrile solvent at 25° C. for 6.5 hours, 11β-fluoro-3-hydroxy-7a-methylestra-1,3,5(10)-triene-17-one can be obtained. However, in this synthetic process, copper (II) bromide is used in an amount of about 2.2 mol per 1 mol of the starting material. Patent Document 1 does not disclose any Synthetic Example wherein a catalytic amount of copper (II) bromide was used.
Non-Patent Document 1 discloses that, in a similar reaction, when copper (II) bromide is used in an amount of less than 1 mol (e.g., 0.9 equivalent) per 1 mol of starting material, the yield of the objective product becomes very low (less than 10%).
Furthermore, Patent Document 2 discloses, in Example 21, a method for producing 7α-methylestrone from 4-estrene-7a-methyl-3,17-dione using copper (II) chloride under an argon atmosphere. However, this is also not an effective method for industrial production in the following respects. In this method, 2 mol of copper (II) chloride is necessary per 1 mol of the starting material. Furthermore, this method requires a long reaction time (72 hours), a troublesome work-up procedure, filtration using expensive silica gel column chromatography for isolation and purification of the objective product, etc. Furthermore, because an excessive amount of copper (II) chloride is necessary in the reaction, i.e., twice that of the starting material in moles, a very large amount of copper waste is generated compared with the amount of the final product, adversely affecting the environment.
As described above, various methods for aromatizing a ring A of a steroid skeleton using a copper halide have been reported. However, a method wherein the ring A is effectively aromatized using only a catalytic amount of copper halide, in particular, a method by which 7α-methylestrone can be produced from 4-estrene-7a-methyl-3,17-dione in an industrially applicable scale and at high yield, has not been reported yet.
Patent Document 1: US Patent Publication No. 2005-90477
Patent Document 2: Japanese Unexamined Patent Publication No. 2001-525855
Non-Patent Document 1: Steroids, 1997, 62, 437-443